Anatomic Pathology / CLEAR CELL ODONTOGENIC CARCINOMA

Clear Cell Odontogenic Carcinoma Report of Two Cases and Review of the Literature Eugenio Maiorano, MD,1 Mario Altini, DDS,2 Giuseppe Viale, MD,3 Adriano Piattelli, MD, DDS,4 and Gianfranco Favia, MD, DDS5 Key Words: Clear cell odontogenic carcinoma; Clear cell ameloblastoma; Odontogenic tumors; Clear cell tumors; Immunohistochemistry

Abstract This study reviews the literature and reports on the morphologic and immunophenotypic features of 2 clear cell odontogenic carcinomas occurring in the mandible of elderly women, showing extensive infiltration into adjacent tissues. The tumor cells were large, with clear cytoplasm, and arranged in irregular sheets. Some of the latter demonstrated a peripheral rim of cells with eosinophilic cytoplasm or included duct-like structures. There was no evidence of ameloblastic differentiation. Most cells contained glycogen granules and were immunoreactive for cytokeratins and epithelial membrane antigen. In the differential diagnosis other clear cell odontogenic, salivary gland, and metastatic tumors should be considered. Both cases were treated with surgical excision, and the patients are free of disease after 3 and 5 years, respectively. In the literature, however, variable behavior of these tumors has been reported, including recurrence and metastases. It is recommended that terms such as clear cell ameloblastoma and clear cell odontogenic tumor not be used to describe such tumors.

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Clear cells are found in many different tumors and usually result from fixation artifacts; intracellular storage of various substances such as glycogen, mucin, or lipid; or paucity of organelles.1 In the maxillofacial area, clear cell tumors usually are salivary2 or odontogenic in origin, although occasionally metastatic tumors need to be considered.3 Odontogenic neoplasms composed entirely or predominantly of clear cells are exceptionally rare.4 Examples include the clear cell variants of calcifying epithelial odontogenic tumor5,6 and of ameloblastoma7-9 and clear cell odontogenic carcinoma.10 The latter has been shown to exhibit aggressive behavior in terms of recurrence or metastases to regional nodes and distant sites.11-14 Consequently, terms such as clear cell odontogenic tumor15-19 and clear cell ameloblastoma20-22 seem inappropriate to identify this rare entity, and most authors now agree that these tumors should be called clear cell odontogenic carcinomas,11-13,23 even if showing occasional ameloblastoma-like histologic patterns.23 A search of the English literature, using clear cell and odontogenic tumor, odontogenic carcinoma, and ameloblastoma as key words, identified 27 unequivocal cases of clear cell odontogenic carcinoma. Owing to the limited numbers of such tumors reported so far, only incomplete data are available on their clinical, immunohistochemical, and prognostic features. The present study was aimed at reporting 2 additional cases of clear cell odontogenic carcinoma (CCOC), focusing on their morphologic, immunophenotypic, and differential diagnostic features. Also, in view of the attenuated malignancy demonstrated by the tumors reported herein, the therapeutic approaches and the prognosis of CCOCs are discussed. Am J Clin Pathol 2001;116:107-114

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Case Reports

Materials and Methods

Case 1

Case 2 An 84-year-old woman was admitted for a lump on the lingual aspect of the mandible, of 6 months’ duration. Panoramic radiographs showed a radiolucent lesion with poorly defined margins of the anterior left mandible. The lesion was multilocular and associated with displaced teeth and apical resorption. The patient underwent conservative hemimandibulectomy and subsequent reconstruction and was free of disease 3 years after the original diagnosis. Both patients underwent extensive workup to rule out the occurrence of occult metastases.

The surgical specimens were fixed in 10% neutral buffered formalin for 12 hours and paraffin-embedded. Five-micrometer-thick sections were cut and stained with H&E, periodic acid–Schiff (PAS) with and without diastase treatment, alcian blue at pH 2.5, mucicarmine, Congo red and Wolman standard toluidine blue (examined under polarized light for the demonstration of amyloid), and Gomori reticulin. Consecutive sections, collected on positively charged slides for capillary gap procedures (Dako, Glostrup, Denmark), were used for the immunohistochemical studies, which were performed with an avidinbiotin/peroxidase complex method in a TecMate 500 Dako Immunostainer (Dako), using the antibodies listed in ❚Table 1❚. Before the incubations with the specific primary antibodies, the sections were treated with 0.01% Pronase E (protease type XIV; Sigma Italia SpA, Milan, Italy) in phosphate-buffered saline for 15 minutes at room temperature or subjected 4 times to a 5-minute microwave irradiation following immersion in a 0.1-mol/L concentration of citrate buffer, pH 6.0, in a microwave oven, set at 750 W, as specified in Table 1. All the incubations lasted 30 minutes at room temperature and were followed by three 3-minute washings in tris(hydroxymethyl)aminomethane buffered saline. Appropriate positive controls (Table 1) were included in the procedures, along with negative controls, which were achieved by substituting nonimmune serum for the primary specific antibodies.

❚Image 1❚ Panoramic radiogram showing a destructive lesion of the anterior mandible. The osteolytic lesion has scalloped borders and includes 2 teeth.

❚Image 2❚ Computed tomography scan of the same patient as in Image 1, demonstrating the infiltrative nature of the lesion that extensively invades the adjacent soft tissues.

An 81-year-old woman had an intraoral nodule of 2 months’ duration. Clinical examination revealed a mandibular lesion causing expansion, without ulceration of the overlying oral mucosa. A panoramic radiograph showed a destructive lesion of the anterior mandible with scalloped borders ❚Image 1❚. The adjacent teeth were displaced, and 2 of them were entrapped within the lesion. Computed tomographic scans demonstrated the infiltrative nature of the lesion, which extensively invaded the adjacent soft tissues ❚Image 2❚. The patient underwent excisional biopsy of the tumor and subsequent conservative anterior mandibulectomy, with preservation of a rim of cortical bone on the lingual aspect of the mandible. The patient was alive with no evidence of recurrence 5 years after the initial diagnosis.

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Anatomic Pathology / ORIGINAL ARTICLE

❚Table 1❚ Antibodies Used for Immunologic Characterization of Clear Cell Odontogenic Carcinomas* Antigen Detected Actin (muscle-specific) CD34 Collagen type IV Cytokeratins Cytokeratins 8-18 Cytokeratin 19 Cytokeratin 34betaE12 Epithelial membrane antigen Hepatocyte antigen Melanoma antigen Myosin (muscle-specific) Prostate-specific antigen S-100 protein Thyroglobulin Vimentin *

Clone HHF 35 Qbend 10 C IV AE1-AE3 CAM 5.2 BA 17 34betaE12 E29 OCH 1E5 HMB 45 SMMS-1 ER-PR8 — — V9

Dilution

Antigen Retrieval

1:200 1:100 1:100 1:100 Neat 1:50 1:50 1:50 1:100 1:400 1:800 1:50 1:300 1:100 1:10

Microwave Microwave Microwave Pronase E Pronase E Pronase E Pronase E Microwave Microwave Microwave Microwave Microwave Pronase E — Microwave

Positive Control Leiomyoma Hemangioma Leiomyoma Breast carcinoma Breast carcinoma Breast carcinoma Prostate Breast carcinoma Liver carcinoma Melanoma Parotid gland Prostate Melanoma Thyroid Leiomyoma

All antibodies were purchased from Dako, Glostrup, Denmark, except anticytokeratin CAM 5.2, which was purchased from Becton Dickinson, Erembogeden-Alst, Belgium. All are monoclonal antibodies with the exception of S-100 protein, which was raised in rabbit. Pronase E, Sigma Italia SpA, Milan, Italy.

Results Histopathologic Features Both tumors had similar morphologic features and will be described together. They consisted of large and irregular sheets or cords of neoplastic cells in a richly cellular, collagenous stroma ❚Image 3❚. The neoplastic cells were cuboidal or polyhedral, with centrally placed, rounded nuclei. Some of the neoplastic clusters showed a peripheral rim of cells with abundant eosinophilic cytoplasm and centrally located clear cells. In other areas, the neoplastic cell population consisted

❚Image 3❚ Clear cell odontogenic carcinoma is composed of irregular sheets of neoplastic epithelial cells immersed in a richly cellular, collagenous stroma. The neoplastic epithelial cells are polyhedral and show distinct cytoplasmic clearing in the center of the neoplastic sheets (H&E, ×100).

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almost entirely of large polyhedral cells with prominent cytoplasmic clearing ❚Image 4❚. Occasionally, the neoplastic nests showed central duct-like structures lined by flattened or cubical cells with moderately eosinophilic cytoplasm ❚Image 5❚. Nuclear pleomorphism and mitotic activity were scanty or absent (